Ab0017 Efficacy of Tocilizumab in Unclassified Auto-Inflammatory Diseases: A Study of 14 Patients

Background: Unclassified Systemic Autoinflammatory Disease (USAID) arises when systemic symptoms and inflammation diverge from criteria for polygenic diseases, like Still's, Schnitzler's, Behçet's, and Sitrame, and lack mutations in genetic analyses. Several hundred patients in France are estimated to suffer from USAID, which can occur from birth or in adulthood and are found worldwide. During flare-ups, patients endure general symptoms (fever, fatigue) and specific manifestations (rashes, mouth ulcers, diarrhea, abdominal pain, joint/muscle pain). Other symptoms include conjunctivitis, uveitis, headaches, and adenopathy. Diagnosis relies on clinical criteria, emphasizing blood inflammation (CRP) during an attack, and ruling out infections. Attacks usually resolve spontaneously over time. However, they recur regularly in the absence of treatment leading to complications, varying by patient and family. Treatment aims to prevent relapses, enhance quality of life, and avert complications. Colchicine may be used if against fever, abdominal pain, and inflammation. Some use anti-cytokine pro-inflammatory biotherapies. Treatment usually aligns with the disease most resembling the patient's symptoms. Objectives: This study explores tocilizumab's use and efficacy in adult USAID patients at the French National Reference Center for Autoinflammatory Diseases (CEREMAIA). Methods: This retrospective study analyzed 227 USAID cases in CEREMAIA since 2015. Results: Of the 1,534 adult patients followed up at CEREMAIA Tenon in Paris for an autoinflammatory disease, 227 had USAID, and 14 of those patients (28% men) had received tocilizumab treatment. The patients included in the study had a median age of 19.57 years at symptom onset and were diagnosed at an average age of 37.07 years [range: 21-49]. There were 3 familial cases (21.43%) and a single consanguineous patient (9.09%). Most of the patients were Caucasian (71.43%) and the rest were of Mediterranean origin. The most frequent clinical manifestations, in descending order, were non-infectious fever (84.62%), arthralgias (78.57%), myalgias (61.54%), digestive symptoms such as abdominal pain (50%), mouth ulcers (42.86%), skin lesions such as urticaria (28.57%) or diffuse erythema (35.71%) or less frequently a pustular rash on the body (7, 14%), ocular symptoms (35.71%), headache (28.57%), adenopathy (21.43%), hepatosplenomegaly or hepatomegaly (21.43%), odynophagia (14.29%), genital aphthae (14.29%), and chest pain without pleurisy (14.29%). Only one patient had renal involvement (7.14%) and no patient had AA amyloidosis. Prior to the initiation of tocilizumab, 9 patients (64.29%) had received corticosteroid treatment, 6 (42.86%) had received colchicine, 12 (92.86%) had received anti-IL1 treatment, 5 (35.71%) had received anti-TNF alpha treatment, and 1 (7.14%) had received anti-JAK treatment. Tocilizumab treatment was initiated at a median age of 39.36 years [24-54]. The intravenous form was administered to 5 patients (35.71%), while the subcutaneous form was administered to 10 patients (76.92%). Dosages included 162 mg weekly for 9 patients, 162 mg every 2 weeks for 1 patient, 8 mg/kg monthly for 3 patients, and 560 mg monthly for 1 patient. Treatment duration was 14 months, and clinical symptom improvement was observed in 57.14%. Currently, 4 patients remain on tocilizumab, while 9 discontinued due to skin intolerance, inefficacy, infection, patient choice, or medical decision. After a median follow-up of 43.57 months, one patient has died. Conclusion: This study suggests tocilizumab as a promising therapeutic option, especially for Still's disease-like symptoms in USAID. A prospective study is recommended to validate these findings. REFERENCES: [1] "Syndrome of Undifferentiated Recurrent Fever (SURF): An Emerging Group of Autoinflammatory Recurrent Fevers". R. Papa and al., 2021. [2] "Clinical characterization, long-term follow-up, and response to treatment of patients with syndrome of undifferentiated recurrent fever (SURF)". F. Sutera and al., 2022. Acknowledgements: We thank all study participants, especially the geneticists who assisted with diagnoses, and the patients who consented to participate. Disclosure of Interests: None declared.